Walker Stephen J, Grant Kathleen A
Integrative Neuroscience Initiative on Alcoholism (INIA: Stress), Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27156, USA.
Alcohol. 2006 Jan;38(1):1-4. doi: 10.1016/j.alcohol.2006.03.008.
The gene SNCA (or NACP), which codes for alpha-synuclein, a small synaptic protein involved in dopaminergic neurotransmission, maps to a quantitative trait locus for alcohol preference and is differentially expressed in specific brain regions in alcohol-preferring versus -nonpreferring rats. Moreover, elevated alpha-synuclein messenger RNA (mRNA) and protein levels in peripheral blood have been shown to be associated with craving in patients with alcoholism. The focus of this study was to evaluate gene expression, including the levels of alpha-synuclein mRNA, in peripheral blood in nonhuman primates that were induced to drink ethanol (4 months) and then allowed 14 months of 22-h/day access to ethanol (4% wt/vol) or water compared to alcohol-naïve controls. Differential gene expression, including alpha-synuclein mRNA levels, was measured in 18 cynomolgus macaque monkeys, 8 that had been chronically self-administering ethanol for 18 months and 10 that were alcohol naïve. Cynomolgus monkeys in this study self-administered ethanol at average rates of between 1.2 and 4.2g/kg/day. This group of ethanol-drinking monkeys had a highly significant 3.21-fold higher level of alpha-synuclein mRNA in peripheral blood than alcohol-naïve controls. These data agree with recent reports of elevated alpha-synuclein mRNA and protein in the blood of human alcoholics, support the concept of an association between alpha-synuclein and alcoholism, and demonstrate, for the first time, a biomarker present in rats, monkeys, and humans for the consumption of ethanol.
基因SNCA（或NACP）编码α-突触核蛋白，这是一种参与多巴胺能神经传递的小突触蛋白，定位于酒精偏好的数量性状基因座，并且在偏好酒精与不偏好酒精的大鼠的特定脑区中差异表达。此外，已表明外周血中α-突触核蛋白信使核糖核酸（mRNA）和蛋白质水平升高与酒精中毒患者的渴望有关。本研究的重点是评估诱导饮用乙醇（4个月），然后给予14个月每天22小时饮用乙醇（4%重量/体积）或水的非人灵长类动物外周血中的基因表达，包括α-突触核蛋白mRNA水平，并与未接触酒精的对照进行比较。在18只食蟹猴中测量了差异基因表达，包括α-突触核蛋白mRNA水平，其中8只长期自我给药乙醇18个月，10只为未接触酒精的。本研究中的食蟹猴以平均每天1.2至4.2克/千克的速率自我给药乙醇。这组饮用乙醇的猴子外周血中α-突触核蛋白mRNA水平比未接触酒精的对照高3.21倍，具有高度显著性。这些数据与近期关于人类酒精中毒患者血液中α-突触核蛋白mRNA和蛋白质升高的报道一致，支持α-突触核蛋白与酒精中毒之间存在关联的概念，并首次证明在大鼠、猴子和人类中存在乙醇消费的生物标志物。
